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Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway 期刊论文

编号：

9cd135fd-81d6-4fad-a4f2-73ca04077d9b
作者：

Lu, Zhihui^[1,2,3,4,5];Song, Nana^[1,2,3,4,5];Shen, Bo(沈波)^[1,2,3,4,5]Xu, XiaLian(徐夏莲)^[1,2,3,4,5]Fang, Yi(方艺)^[1,2,3,4,5]Shi, Yiqin^[1,2,3,4,5];Ning, Yichun^[1,2,3,4,5];Hu, Jiachang(胡家昌)^[1,2,3,4,5]Dai, Yan^[1,2,3,4,5];Ding, Xiaoqiang(丁小强)^[1,2,3,4,5]Zou, Jianzhou(邹建洲)*^[1,2,3,4,5]Teng, Jie(滕杰)*^[1,2,3,4,5]
语种：

英文
期刊：

TRANSPLANTATION ISSN：0041-1337 2018 年 102 卷 7 期 (E331 - E344) ; JUL
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摘要：

Background The hepatocyte growth factor (HGF) target pathway plays pivotal renoprotective roles after acute kidney injury. Syndecan-1 (SDC-1) serves as the coreceptor for HGF. Shedding of SDC-1 is involved in various pathological processes. Thus, we hypothesized that ischemia/reperfusion injury induced SDC-1 shedding, and inhibiting SDC-1 shedding would protect against kidney injury by potentiating activation of the HGF receptor mesenchymal epithelial transition factor (c-Met).
Methods Expression of SDC-1 and its sheddases were observed in kidneys of sham and ischemia/reperfusion (I/R) mice. To inhibit SDC-1 shedding, mice were injected with the sheddase inhibitor GM6001 before I/R surgery, and then, renal inflammation, tubular apoptosis, and activation of the c-Met/AKT/glycogen synthase kinase-3 (GSK-3) pathway were analyzed. In vitro, human proximal tubular cell lines were pretreated with GM6001 under hypoxia/reperfusion conditions. The apoptosis and viability of cells and expression of c-Met/AKT/GSK-3 pathway components were evaluated. The relationship was further confirmed by treatment with SU11274, a specific inhibitor of phospho-c-Met.
Results Shedding of SDC-1 was induced after ischemia/reperfusion injury both in vivo and in vitro. GM6001 pretreatment suppressed SDC-1 shedding, alleviated renal inflammation and tubular apoptosis, and upregulated phosphorylation of the c-Met/AKT/GSK-3 pathway. In vitro, pretreatment with GM6001 also decreased hypoxia/reperfusion-induced cell apoptosis and promoted activation of the c-Met pathway. In addition, the cytoprotective role of GM6001 was attenuated by suppressing c-Met phosphorylation with SU11274.
Conclusions Our findings suggest that inhibiting I/R-induced SDC-1 shedding protected against ischemic acute kidney injury by potentiating the c-Met/AKT/GSK-3 pathway.
推荐引用方式
GB/T 7714：

Lu Zhihui,Song Nana,Shen Bo, et al. Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway [J].TRANSPLANTATION,2018,102(7):E331-E344.
APA：

Lu Zhihui,Song Nana,Shen Bo,Xu XiaLian,&Teng Jie.(2018).Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway .TRANSPLANTATION,102(7):E331-E344.
MLA：

Lu Zhihui, et al. "Syndecan-1 Shedding Inhibition to Protect Against Ischemic Acute Kidney Injury Through HGF Target Signaling Pathway" .TRANSPLANTATION 102,7(2018):E331-E344.
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